Pembrolizumab for the treatment of patients with Bacillus Calmette-Guérin unresponsive, high-risk non–muscle-invasive bladder cancer: over two years follow-up of KEYNOTE-057


Pembrolizumab ( Keytruda ) was approved for the treatment of high-risk ( HR ) non–muscle-invasive bladder cancer ( NMIBC ) based on results from the phase 2 KEYNOTE-057 trial.

Researchers have presented safety, efficacy, and posttreatment outcomes with 2 years or more follow-up from KEYNOTE-057 cohort A.

Patients with histologically confirmed high-risk Bacillus Calmette-Guérin ( BCG )-unresponsive carcinoma in situ ( CIS ) with or without papillary tumors who received adequate BCG therapy and were ineligible for or opted out of radical cystectomy ( RC ) received Pembrolizumab 200 mg Q3W for up to 2 years or until disease recurrence, progression, or unacceptable toxicity.

The primary endpoint was complete response rate ( CRR ). Key secondary endpoints were duration of response ( DOR ) and safety.

Overall, 102 patients were initially enrolled, and 96 were included in the efficacy analysis. Median time from enrollment to data cut off was 28.4 months ( range, 18.2-40.5 ).

Complete response rate was 40.6% ( 95% CI, 30.7-51.1 ), and median duration of response was 16.2 months ( range, 0+ to 30.4+ ).

Among 39 patients with complete response, 18 ( 46.2% ) had a DOR greater than or equal to 12 months.

No patient’s disease progressed to muscle-invasive or metastatic bladder cancer while on study treatment.

Median progression-free survival ( PFS ) and overall survival ( OS ) were not reached.
At 12 months, PFS was 82.7% and OS was 97.9%.

A total of 36 patients (37.5%) underwent radical cystectomy after discontinuation from study treatment, which included 9 of 22 patients ( 40.9% ) who had recurrence after initial complete response and 27 of 57 ( 47.4% ) nonresponders.
Of the 36 who underwent radical cystectomy, 33 ( 91.6% ) had no pathological upstaging to MIBC and 3 ( 8.3% ) had at least pT2 disease at time of radical cystectomy.

For subsequent treatments other than radical cystectomy, 27 of 96 ( 28.1% ) patients received additional intravesical therapy ( eg, BCG, Gemcitabine, or Mitomycin ), 21 of 96 ( 21.9% ) underwent local procedures ( eg, TURBT ), and 3 of 96 ( 3.1% ) received systemic therapy ( eg, Pembrolizumab ).

In 102 patients treated with Pembrolizumab, treatment-related adverse effects ( TRAEs ) occurred in 67 ( 65.7% ) patients; most frequently reported TRAEs were fatigue, pruritus, and diarrhea ( 10.8% each ).
Grade 3/4 TRAEs occurred in 13 patients ( 12.7% ), and 21 patients ( 20.6% ) experienced immune-mediated adverse effects. There were no grade 5 TRAEs.

In conclusion, after more than 2 years of follow-up, durable and clinically meaningful activity of Pembrolizumab was observed in patients who had high-risk BCG-unresponsive carcinoma in situ with or without papillary tumors and who were ineligible for or opted out of radical cystectomy.
Pembrolizumab did not seem to limit the opportunity for subsequent therapies, including radical cystectomy.
The safety profile was consistent with what is reported in the literature. ( Xagena )

Source: American Society of Clinical Oncology ( ASCO ) Virtual Meeting, 2020

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